Heart rate variability in chronic ischemic stroke: analysis during the sleep-wake cycle

Abstract

Background Alterations of the autonomic nervous system (ANS) in the chronic stage of ischemic stroke (IS) are not well understood. Heart rate variability (HRV) provides a noninvasive approach to assess autonomic function.

Objective To compare the HRV parameters during the sleep-wake cycle between patients with IS in the chronic stage and healthy subjects.

Methods We conducted a retrospective transversal study based on clinical records and 24-hour electrocardiogram (EKG) monitoring registries of 179 patients with a confirmed IS diagnosis and 184 age- and sex-matched healthy subjects. Circadian variation was calculated according to the variation of the total autonomic activity (VTAI) and the parasympathetic activity (VPAI) indexes. Comparisons were performed using nonparametric tests. Multivariable analyses were performed with canonical discriminant analysis (CDA) and a three-way analysis of variance (ANOVA). Statistical significance was established with a confidence level of 95%.

Results During waking hours, the healthy group exhibited higher variability in the time domain and frequency domain parameters: standard deviation of NN intervals (SDNN, p < 0.001) and of the average NN intervals (SDANN, p < 0.001), as well as low-frequency (LF) band (p < 0.001). During sleep, the difference was higher in the high-frequency (HF) band (p < 0.001), and lower in the low-/high-frequency ratio (LF/HF, p < 0.001). Both VPAI and VTAI showed less significant difference in IS patients (p < 0.001).

Conclusion There was diminished heart vagal activity among IS patients, as measured through HRV. During sleep, this is likely caused by an imbalance in the sympathetic and parasympathetic systems shifting through the sleep phases. These imbalances could persist over time in patients with IS, lasting months after the initial injury.

Resumo

Antecedentes A compreensão das alterações do sistema nervoso autônomo (SNA) na fase crônica do acidente vascular cerebral isquêmico (AVCi) ainda é insuficiente. A variabilidade da frequência cardíaca (VFC) fornece uma abordagem não invasiva para avaliar a função autonômica.

Objetivo Comparar os parâmetros da VFC durante o ciclo sono-vigília entre participantes saudáveis e com AVCi crônico.

Métodos Estudo retrospectivo transversal baseado em registros clínicos e registros de eletrocardiograma de 24 horas de 179 pacientes com AVCi confirmado e 184 controles pareados por idade e sexo. As variações do índice de atividade autonômica total (VTAI) e do índice de atividade parassimpática (VPAI) foram usados para calcular a variação circadiana. As comparações foram feitas usando testes não paramétricos. Análise discriminante canônica (CDA) e análise de variância (ANOVA) de três vias foram usadas para análises multivariadas. Um nível de confiança de 95% foi estabelecido para a significância estatística.

Resultados O grupo controle exibiu maior variabilidade nos parâmetros de domínio do tempo e da frequência durante as horas de vigília: desvio padrão dos intervalos NN (SDNN, p < 0,001) e das médias dos intervalos NN (SDANN, p < 0,001), assim como a banda de baixa frequência (LF, p < 0,001). Durante o sono, a diferença foi maior na banda de alta frequência (HF, p < 0,001) e a razão baixa/alta frequência (LF/HF) foi menor (p < 0,001). O VPAI e VTAI mostraram menor variabilidade nos pacientes com AVC (p < 0,001).

Conclusão Os pacientes com AVCi apresentaram atividade vagal cardíaca diminuída, medida pela VFC. Isto pode resultar de desequilíbrios nos sistemas simpático e parassimpático que mudam durante as fases do sono. Em pacientes com AVCi, esses desequilíbrios podem permanecer meses após a lesão inicial.

Keywords

Ischemic Stroke - Heart Rate Determination - Autonomic Nervous System - Stroke - Circadian Rhythm

Palavras-chave

Acidente Vascular Cerebral Isquêmico - Determinação da Frequência Cardíaca - Sistema Nervoso Autônomo - Acidente Vascular Cerebral - Ritmo Circadiano

Authors' Contributions

NBR: contributed to the conception and design of the work, the acquisition, analysis, and interpretation of the data, the drafting of the article, and the final approval of the version to be published; FDC: contributed to the conception and design of the study, the acquisition of data, and writing of the manuscript; JF: contributed through data interpretation, statistical analysis, and writing of the manuscript; GSS: contributed to the conception and design of the study, the acquisition of data, and writing of the manuscript. The authors complied with the International Committee of Medical Journal Editors Criteria for Authorship.

Editor-in-Chief: Ayrton Roberto Massaro.

Associate Editor: Octávio Marques Pontes-Neto.

Publikationsverlauf

Eingereicht: 04. Februar 2024

Angenommen: 27. Juli 2024

Artikel online veröffentlicht:
06. November 2024

• References

• 1 GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021; 20 (10) 795-820
• 2 Kernan WN, Viera AJ, Billinger SA. et al; American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease. Primary Care of Adult Patients After Stroke: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke 2021; 52 (09) e558-e571
• 3 Ahmed R, Mhina C, Philip K. et al. Age- and Sex-Specific Trends in Medical Complications After Acute Ischemic Stroke in the United States. Neurology 2023; 100 (12) e1282-e1295
• 4 Tahsili-Fahadan P, Geocadin RG. Heart-Brain Axis: Effects of Neurologic Injury on Cardiovascular Function. Circ Res 2017; 120 (03) 559-572
• 5 Leppert MH, Sillau S, Lindrooth RC, Poisson SN, Campbell JD, Simpson JR. Relationship between early follow-up and readmission within 30 and 90 days after ischemic stroke. Neurology 2020; 94 (12) e1249-e1258
• 6 Billman GE, Huikuri HV, Sacha J, Trimmel K. An introduction to heart rate variability: methodological considerations and clinical applications. Front Physiol 2015; 6: 55 . Doi: 10.3389%2Ffphys.2015.00055
• 7 Singh N, Moneghetti KJ, Christle JW, Hadley D, Froelicher V, Plews D. Heart Rate Variability: An Old Metric with New Meaning in the Era of Using mHealth technologies for Health and Exercise Training Guidance. Part Two: Prognosis and Training. Arrhythm Electrophysiol Rev 2018; 7 (04) 247-255
• 8 Freeman R, Chapleau MW. Testing the autonomic nervous system. Handb Clin Neurol 2013; 115: 115-136
• 9 Cheshire Jr WP. Autonomic History, Examination, and Laboratory Evaluation. Continuum (Minneap Minn) 2020; 26 (01) 25-43
• 10 Kumar S, Selim MH, Caplan LR. Medical complications after stroke. Lancet Neurol 2010; 9 (01) 105-118
• 11 Seifert F, Kallmünzer B, Gutjahr I. et al. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke. J Neurol 2015; 262 (05) 1182-1190
• 12 Sposato LA, Hilz MJ, Aspberg S. et al; World Stroke Organisation Brain & Heart Task Force. Post-Stroke Cardiovascular Complications and Neurogenic Cardiac Injury: JACC State-of-the-Art Review. J Am Coll Cardiol 2020; 76 (23) 2768-2785
• 13 Sassi R, Cerutti S, Lombardi F. et al. Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society. Europace 2015; 17 (09) 1341-1353
• 14 Francica JV, Bigongiari A, Mochizuki L. et al. Cardiac autonomic dysfunction in chronic stroke women is attenuated after submaximal exercise test, as evaluated by linear and nonlinear analysis. BMC Cardiovasc Disord 2015; 15: 105 Doi: 10.1186%2Fs12872-015-0099-9
• 15 Grilletti JVF, Scapini KB, Bernardes N. et al. Impaired baroreflex sensitivity and increased systolic blood pressure variability in chronic post-ischemic stroke. Clinics (Sao Paulo) 2018; 73: e253
• 16 Quintana DS. Statistical considerations for reporting and planning heart rate variability case-control studies. Psychophysiology 2017; 54 (03) 344-349
• 17 Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 1996; 93 (05) 1043-1065
• 18 Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health 2017; 5: 258
• 19 Li K, Rüdiger H, Ziemssen T. Spectral Analysis of Heart Rate Variability: Time Window Matters. Front Neurol 2019; 10: 545
• 20 Tobaldini E, Nobili L, Strada S, Casali KR, Braghiroli A, Montano N. Heart rate variability in normal and pathological sleep. Front Physiol 2013; 4: 294
• 21 Cintra F, Poyares D, DO Amaral A. et al. Heart rate variability during sleep in patients with vasovagal syncope. Pacing Clin Electrophysiol 2005; 28 (12) 1310-1316
• 22 Eckberg DL. Sympathovagal balance: a critical appraisal. Circulation 1997; 96 (09) 3224-3232
• 23 Kasner SE, Chalela JA, Luciano JM. et al. Reliability and validity of estimating the NIH stroke scale score from medical records. Stroke 1999; 30 (08) 1534-1537
• 24 Lavine BK, Rayens WS. Statistical Discriminant Analysis. In: Comprehensive Chemometrics [Internet]. Elsevier; 2009. [cited 2024 Jul 4]. p. 517–40. Available at: https://linkinghub.elsevier.com/retrieve/pii/B9780444527011000247
• 25 Dorrance AM, Fink G. Effects of Stroke on the Autonomic Nervous System. Compr Physiol 2015; 5 (03) 1241-1263
• 26 Dütsch M, Burger M, Dörfler C, Schwab S, Hilz MJ. Cardiovascular autonomic function in poststroke patients. Neurology 2007; 69 (24) 2249-2255
• 27 Jimenez-Ruiz A, Racosta JM, Kimpinski K, Hilz MJ, Sposato LA. Cardiovascular autonomic dysfunction after stroke. Neurol Sci 2021; 42 (05) 1751-1758
• 28 Cygankiewicz I, Zareba W. Heart rate variability. Handb Clin Neurol 2013; 117: 379-393
• 29 Tobaldini E, Proserpio P, Oppo V. et al. Cardiac autonomic dynamics during sleep are lost in patients with TIA and stroke. J Sleep Res 2020; 29 (03) e12878
• 30 Chen Z, Venkat P, Seyfried D, Chopp M, Yan T, Chen J. Brain-Heart Interaction: Cardiac Complications After Stroke. Circ Res 2017; 121 (04) 451-468
• 31 Gujjar AR, Sathyaprabha TN, Nagaraja D, Thennarasu K, Pradhan N. Heart rate variability and outcome in acute severe stroke: role of power spectral analysis. Neurocrit Care 2004; 1 (03) 347-353
• 32 Sposato LA, Riccio PM, Hachinski V. Poststroke atrial fibrillation: cause or consequence? Critical review of current views. Neurology 2014; 82 (13) 1180-1186
• 33 Tse G, Lai ET, Tse V, Yeo JM. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus. J Diabetes Res 2016; 2016: 2848759 . Doi: 10.1155%2F2016%2F2848759
• 34 May AM, Van Wagoner DR, Mehra R. OSA and Cardiac Arrhythmogenesis: Mechanistic Insights. Chest 2017; 151 (01) 225-241
• 35 Scheitz JF, Nolte CH, Doehner W, Hachinski V, Endres M. Stroke-heart syndrome: clinical presentation and underlying mechanisms. Lancet Neurol 2018; 17 (12) 1109-1120
• 36 Aftyka J, Staszewski J, Dębiec A, Pogoda-Wesołowska A, Żebrowski J. Heart rate variability as a predictor of stroke course, functional outcome, and medical complications: A systematic review. Front Physiol 2023; 14: 1115164
• 37 Karemaker JM. An introduction into autonomic nervous function. Physiol Meas 2017; 38 (05) R89-R118
• 38 Germán-Salló Z, Germán-Salló M. Non-linear Methods in HRV Analysis. Procedia Technol 2016; 22: 645-651
• 39 Ishaque S, Khan N, Krishnan S. Trends in Heart-Rate Variability Signal Analysis. Front Digit Health 2021; 3: 639444
• 40 Cantú-Brito C, Sampaio Silva G, Ameriso SF. Embolic Stroke of Undetermined Source in Latin America: A Review. Neurologist 2017; 22 (05) 171-181
• 41 Perera KS, Swaminathan B, Veltkamp R. et al. Frequency and features of embolic stroke of undetermined source in young adults. Eur Stroke J 2018; 3 (02) 110-116 Doi: 10.1177%2F2396987318755585
• 42 Raphaely Beer N, Soroker N, Bornstein NM, Katz-Leurer M. The cardiac autonomic nervous system response to different daily demands among patients at the sub-acute phase post ischemic stroke and healthy controls. NeuroRehabilitation 2018; 42 (04) 391-396
• 43 Brunetti V, Vollono C, Testani E, Pilato F, Della Marca G. Autonomic Nervous System Modifications During Wakefulness and Sleep in a Cohort of Patients with Acute Ischemic Stroke. J Stroke Cerebrovasc Dis 2019; 28 (06) 1455-1462
• 44 Belli TR, Souza LAPS, Bazan SGZ, Bazan R, Luvizutto GJ. Effects of rehabilitation programs on heart rate variability after stroke: a systematic review. Arq Neuropsiquiatr 2021; 79 (08) 724-731
• 45 Zhao M, Guan L, Wang Y. The Association of Autonomic Nervous System Function With Ischemic Stroke, and Treatment Strategies. Front Neurol 2020; 10: 1411
• 46 Khot SP, Morgenstern LB. Sleep and Stroke. Stroke 2019; 50 (06) 1612-1617
• 47 Mc Carthy CE, Yusuf S, Judge C. et al; for INTERSTROKE. Sleep Patterns and the Risk of Acute Stroke: Results From the INTERSTROKE International Case-Control Study. Neurology 2023; 100 (21) e2191-e2203